MALARIA PARASITE-DERIVED VESICLES ASSOCIATEWITH THE NF-kB SIGNALING PATHWAY

Our ability to cure infectious diseases is greatly limited by a lack of understanding of the way many pathogens evade the human innate immune system. This is indeed the case when it comes to the parasite Plasmodium falciparum (P. falciparum), the leading infectious agent of Malaria, one of the most devastating infectious diseases in humans. It was recently discovered that while being entirely enclosed within the membranes of its host human red blood cells, these parasites can exchange active cargo inter-cellularly among them via secreted extracellular vesicles (EVs). These EVs contain parasite and host proteins and RNA and parasite gDNA. It has been shown that the host monocyte uptake of early stage (ring)-derived parasite vesicles triggers the activation of the DNA-sensing pathway within these immune cells. Here, we provide the evidence that internalization of late stage (trophozoite). P. falciparum-derived EVs by monocytes prompts the activation of a known master regulator transcription factor, nuclear factor kappa B (NF-kB). The activated NF-kB is then translocated to the nucleus to induce transcription of a target genes. As NF-kB is a coordinator of innate and adaptive immune responses, and is involved in cellular signaling of several RNA sensors, such as RIG-I and TLR’s, our finding opens a new line of investigation concerning the function of the vesicle RNA cargo. Our newly discovered crosstalk mechanism strongly supports the existence of a `manipulation strategy` of the host immune environment by the falciparum parasite.